Neglected tropical diseases: progress and expectations
Authors: Faith Feranmi Folahan
Journal: The Lancet Microbe (2023)

To mark World Neglected Tropical Disease (NTD) Day, on Jan 30, 2023, this News piece highlights some progress made over the past 3 years in the fight against NTDs. In 2021, WHO published its second road map for neglected tropical diseases (NTDs), setting targets for the prevention, control, elimination, and eradication of these diseases for the 2021–30 decade and following the 2011–20 edition. These two road maps have underpinned the successes recorded against NTDs in the past 12 years. As of December 2022, 47 countries have successfully eliminated at least one NTD, of which eight were validated or certified in 2022. Cohesive commitment of health agencies, pharmaceutical companies, research institutions, donor countries and other partners to intensify the implementation of integrated programmes such as mass drug administration, vector control, surveillance, case detection, and treatment contributed to reducing the burden, morbidity, and mortality of NTDs in the last decade. Ibrahima Socé Fall (Department of Control of Neglected Tropical Diseases, WHO, Geneva, Switzerland) told The Lancet Microbe, “Over the past decade, the number of people requiring NTD interventions has decreased by 25%, falling by some 80 million people between 2020 and 2021 alone. The burden of disease calculated in disability-adjusted life years (DALYs) is also steadily decreasing. More than one billion people were treated every year for 4 consecutive years between 2016 and 2019 and, although disrupted by the COVID-19 the pandemic, NTD programmes were able to deliver treatment to 800 million people in 2020 and 900 million in 2021”. In addition to these successes, 2022 was marked by some notable developments in NTD research. First, on Nov 29, 2022, The Lancet Infectious Diseases published the results of a phase 2/3 trial of acoziborole for the treatment of human African trypanosomiasis caused by Trypanosoma brucei gambiense (gambiense HAT; also known as sleeping sickness), a disease that can progress from an early haemolymphatic stage to a late meningoencephalitic stage that is fatal if left untreated. The trial was done in the Democratic Republic of the Congo and Guinea and enrolled individuals aged 15 years or older. 159 of 167 patients with late-stage gambiense HAT were successfully treated according to WHO criteria. “A single 960 mg dose of acoziborole administered orally before meal showed an average 95·2% [95% CI 91·2–97·7] efficacy in patients with late-stage gambiense HAT”, said lead investigator Antoine Tarral (Drugs for Neglected Diseases initiative, Geneva, Switzerland). These results are promising because usually individuals with HAT-positive rapid tests must undergo confirmatory tests before commencement of the currently recommended treatment (pentamidine, nifurtimox–eflornithine, or fexinidazole, depending on the disease stage), which is time consuming and requires most patients to travel long distances. “It is a revolution for health-care workers and communities, because this new drug can be administered using a screen-and-treat approach. Patients with HAT-positive rapid blood tests can take acoziborole. It is safe, easy to use, and does not require long treatment procedure, which patients often fail to adhere to”, commented Tarral. Should acoziborole eventually receive regulatory approval, it is likely to increase the quality of response and intervention for gambiense HAT; public health agencies in endemic, low-income countries and remote areas that lack adequate health-care facilities would be able to use this simple treatment, which does not require hospitalisation, invasive diagnosis, or prolonged monitoring. Second, a new benzoxaborole compound (AN15368) was found to be efficacious and safe for the treatment of Chagas disease, a parasitic disease caused by the protozoan Trypanosoma cruzi, in non-human primates. Chagas disease is a potentially life-threatening disease affecting over 7 million people globally, primarily in Latin America. Previous treatment options for humans have some adverse effects and often require continuous use for long periods. “In more than 50 years, the first ever compound discovered to be highly effective for the treatment of T cruzi is benzoxaborale AN15368”, Rick Tarleton (University of Georgia, Athens, GA, USA), who led the research, told The Lancet Microbe. “It is the only compound, also, that has shown incontrovertible and consistent cure of long-term naturally acquired infections with various genetic types of T cruzi in non-human primates”, he added. With no evidence of acute toxicity, long-term implications, or adverse effects on reproduction, AN15368 is a promising candidate for treatment of Chagas disease in people. “AN15368 is orally bioactive and exhibited no overt toxicity in a 60-day course of treatment in non-human primates. Hence, it is a very strong candidate to ultimately progress into human clinical trials”, Tareton concluded. Third, a phase 2 trial of amoxicillin and clavulanate co-administered with rifampicin plus clarithromycin for the treatment of Buruli ulcer is ongoing. Buruli ulcer is a disease of the skin and soft tissue caused by Mycobacterium ulcerans, which can cause long-term morbidity. The disease is generally treated with rifampicin and clarithromycin, but recovery can take up to a year. Preliminary evidence suggests that the addition of amoxicillin and clavulanate to the standard treatment could shorten the duration of treatment from 8 weeks to 4 weeks and accelerate healing. Fourth, in December 2022, the European Medicines Agency (EMA) validated for review Merck and the Pediatric Praziquantel Consortium's application for arprazinquantel for the treatment of schistosomiasis in children aged 3 months to 6 years. Children in this age group are excluded from mass administration of prazinquantel (the drug approved by WHO for the treatment of schistosomiasis) and currently no paediatric treatment option is available despite data from 2020 indicating that over 50 million preschool children live with schistosomiasis globally. “Our efforts with partners, experts, and funders are ongoing to ensure that every young patient suffering from schistosomiasis is treated as soon as possible”, stated Jutta Reinhard-Rupp (Global Health Institute, Merck, Eysins, Switzerland) in a press briefing. Arpraziquantel is an oral dispersible tablet derived from prazinquantel and the efficacy of a single dose administered to children aged 3 months to 6 years was investigated in a phase 3 trial. The results of the trial have not been published in a peer-reviewed journal yet, but announcements at a press release in November 2021 indicated an average cure rate of 90% for both Schistosoma mansoni and Schistosoma haematobium. EMA's approval of arprazinquantel, if granted, would facilitate regulatory decisions for use of the drug in endemic countries. Reinhard-Rupp commented, “I am thrilled and proud that we achieved this result after an intense 10 year-period of collaborative efforts. The goal is to improve children's health by providing a suitable treatment option for these young children who live with schistosomiasis and cannot receive treatment until they attain a certain age”. Finally, in June 2022, WHO updated the 2010 recommendations for treatment of visceral leishmaniasis in patients who are co-infected with HIV, particularly in east Africa and southeast Asia, incorporating knowledge derived from studies done in India and Ethiopia over the past decade. The new guidelines are likely to improve both access to treatment and treatment outcomes. These positive developments will contribute to achieving the goals outlined in the WHO NTD road map. “The NTD road map published in 2021 includes a diverse set of indicators (overarching, cross-cutting, disease-specific) that enable tracking the progress towards improved health outcomes and stronger NTD programmes within the context of universal health coverage, and fine-tuning action as required. I believe if we Act Now, Act Together and we do invest in NTDs then we will reach the targets set out in the NTD road map”, said Socé Fall in his concluding remarks. By 2030, more of these diseases are hoped to be firmly under control, eliminated, or eradicated permanently. For Ending the neglect to attain the Sustainable Development Goals: A road map for neglected tropical diseases 2021–2030 see https://www.who.int/publications/i/item/9789240010352For more on the phase 3 trial of arpraziquantel see https://www.merckgroup.com/en/news/phase-three-results-for-arpraziquantel-16-11-2021.htmlFor more on the phase 2/3 trial of acoziborole see Articles Lancet Infect Dis 2022; published online Nov 29. https://doi.org/10.1016/S1473-3099(22)00660-0For more on AN15368 see Nat Microbiol 2022; 7: 1536–46.For more on the phase 2 trial for Buruli ulcer treatment see Trials 2022; 23: 559.For more on the validation for review of arprazinquantel see https://www.merckgroup.com/en/news/global-health-ema-validation-arpraziquantel-02-12-2022.htmlFor WHO's guidelines for treatment of visceral leishmaniasis see https://www.who.int/news/item/08-06-2022-visceral-leishmaniasis-and-HIV-coinfection-WHO-publishes-new-guideline-with-region-specific-treatment-recommendations For Ending the neglect to attain the Sustainable Development Goals: A road map for neglected tropical diseases 2021–2030 see https://www.who.int/publications/i/item/9789240010352 For more on the phase 3 trial of arpraziquantel see https://www.merckgroup.com/en/news/phase-three-results-for-arpraziquantel-16-11-2021.html For more on the phase 2/3 trial of acoziborole see Articles Lancet Infect Dis 2022; published online Nov 29. https://doi.org/10.1016/S1473-3099(22)00660-0 For more on AN15368 see Nat Microbiol 2022; 7: 1536–46. For more on the phase 2 trial for Buruli ulcer treatment see Trials 2022; 23: 559. For more on the validation for review of arprazinquantel see https://www.merckgroup.com/en/news/global-health-ema-validation-arpraziquantel-02-12-2022.html For WHO's guidelines for treatment of visceral leishmaniasis see https://www.who.int/news/item/08-06-2022-visceral-leishmaniasis-and-HIV-coinfection-WHO-publishes-new-guideline-with-region-specific-treatment-recommendations